Fatemeh Memari1,2, Vahid Tavakolpour3,4, Nasrin Mohajeri1, Behzad Poopak5, Parviz Fallah6, Effat Alizadeh1, Fatemeh Kouhkan7, Nosratollah Zarghami8,9,10. 1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Stem Cells and Regenerative Medicine, Faculty of Medicine Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. 4. Stem Cell Technology Research Center, P.O. Box: 15856-36473, 15856-36473, Tehran, Iran. 5. Medical Science Branch, Islamic Azad University of Tehran, Tehran, Iran. 6. Checkup Clinical and Specialty Laboratory, Karaj, Iran. 7. Stem Cell Technology Research Center, P.O. Box: 15856-36473, 15856-36473, Tehran, Iran. f.kouhkan@stemcellstech.com. 8. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Zarghami@tbzmed.ac.ir. 9. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, 51666-14766, Tabriz, Iran. Zarghami@tbzmed.ac.ir. 10. Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey. Zarghami@tbzmed.ac.ir.
Abstract
BACKGROUND: Acute leukemia involving lymphocytic and myeloid cells is cancer with a high mortality rate. Swift and timely diagnosis might be a potential approach to improving patient prognosis and survival. The microRNA (miRNA) signatures are emerging nowadays for their promising diagnostic potential. MiRNA levels from bone marrow can be used as prognostic biomarkers. METHODS: The current study was designed to evaluate if the microRNAs and tumor suppressor genes (TSGs) profiling of hematopoietic bone marrow could help in acute leukemia early detection. Also, we assessed the DNA methyltransferase 3A (DNMT3A) expression and its possible epigenetic effects on miRNAs plus TSGs expression levels. The expression levels of ten miRNAs and four TSGs involved in acute lymphocytic leukemia (ALL) as well as acute myeloid leukemia (AML) were quantified in 43 and 40 bone marrow samples of ALL and AML patients in comparison with cancer-free subjects via real-time quantitative PCR (RT-qPCR). The receiver-operating-characteristic (ROC) analysis of miRNAs was performed in the study groups. Further, the correlation between the DNMT3A and TSGs was calculated. RESULTS: Significant differences were detected in the bone marrow expression of miRNAs and TSGs (P < 0.05) between acute leukemia patients and healthy group. ROC analysis confirmed the ability of miR-30a, miR-101, miR-132, miR-129, miR-124, and miR-143 to discriminate both ALL and AML patients with an area under the ROC curve of ≥ 0.80 (P < 0.001) and high accuracy. The correlation between DNMT3A and P15/P16 TSGs revealed that DNMT3A plays a vital role in epigenetic control of TSGs expression. Our findings indicated that the downregulation of bone marrow miRNAs and TSGs was accompanied by acute leukemia development. CONCLUSIONS: The authors conclude that this study could contribute to introducing useful biomarkers for acute leukemia diagnosis.
BACKGROUND: Acute leukemia involving lymphocytic and myeloid cells is cancer with a high mortality rate. Swift and timely diagnosis might be a potential approach to improving patient prognosis and survival. The microRNA (miRNA) signatures are emerging nowadays for their promising diagnostic potential. MiRNA levels from bone marrow can be used as prognostic biomarkers. METHODS: The current study was designed to evaluate if the microRNAs and tumor suppressor genes (TSGs) profiling of hematopoietic bone marrow could help in acute leukemia early detection. Also, we assessed the DNA methyltransferase 3A (DNMT3A) expression and its possible epigenetic effects on miRNAs plus TSGs expression levels. The expression levels of ten miRNAs and four TSGs involved in acute lymphocytic leukemia (ALL) as well as acute myeloid leukemia (AML) were quantified in 43 and 40 bone marrow samples of ALL and AML patients in comparison with cancer-free subjects via real-time quantitative PCR (RT-qPCR). The receiver-operating-characteristic (ROC) analysis of miRNAs was performed in the study groups. Further, the correlation between the DNMT3A and TSGs was calculated. RESULTS: Significant differences were detected in the bone marrow expression of miRNAs and TSGs (P < 0.05) between acute leukemia patients and healthy group. ROC analysis confirmed the ability of miR-30a, miR-101, miR-132, miR-129, miR-124, and miR-143 to discriminate both ALL and AML patients with an area under the ROC curve of ≥ 0.80 (P < 0.001) and high accuracy. The correlation between DNMT3A and P15/P16 TSGs revealed that DNMT3A plays a vital role in epigenetic control of TSGs expression. Our findings indicated that the downregulation of bone marrow miRNAs and TSGs was accompanied by acute leukemia development. CONCLUSIONS: The authors conclude that this study could contribute to introducing useful biomarkers for acute leukemia diagnosis.